Nerve injuries are among the most difficult injuries to heal because under normal physiological conditions, mature neurons do not undergo cell division. However, under certain conditions nerve fibers can regenerate across gaps. Injuries that result in long gaps can require surgical intervention, which may include the insertion of a nerve graft or guidance channel.
The current standard of care for surgical intervention in peripheral nerve injuries is the autologous graft. However, this procedure can present several drawbacks including additional surgery, size mismatch, possible neuropathy at the graft site, and the formation of painful neuromas. An alternative to grafting is the use of a nerve guidance channel (suture-able device that creates a channel connecting the distal and proximal ends of the damaged nerve).
Several nerve guidance channel (NGC) devices have been approved for clinical use by the FDA, but to date the majority of these devices have not been able to match the functional recovery of traditional nerve grafting procedures. These devices can be made of synthetic or natural polymers and may be resorbable or non-resorbable. The current generation of approved devices provides necessary passive support to injured nerves through entubulation, which can aid in physical guidance of outgrowing neurites and prevents ingrowth of fibrotic tissues. In designing improved NGCs, the goal is to incorporate biologically active factors that can provide additional cues and support in the hopes of achieving improved recovery.
Peripheral nerve regeneration follows a predictable pattern of four phases over several weeks. Briefly, upon injury, severed nerve stumps initiate repair by releasing a protein-rich exudate into the local environment. This exudate contains growth factors necessary for encouraging regeneration. In the second phase, a fibrin matrix can be established to link the distal and proximal nerve stumps. Fibroblasts migrate into the fibrin matrix from both stumps. In the subsequent phase shwann cells migrate along this matrix. By the second week axons begin to grow along in contact with shwann cells. In the final step to recovery, axons extend into the proximal stump and restore nerve connections, resulting in functional nerve recovery. An ideal NGC would be designed to take advantage of these phases. A further consideration is that to enhance regeneration, it is necessary to minimize the period of Wallerian degeneration (the process by which axonal segments that are severed distal to the soma of the cell break down and lose the ability to become electrically excited). The four main factors that govern Wallerian degeneration:                Existence of shwann cells (which can guide axonal growth cone)        Presence of growth factors that promote regeneration        Presence of basal lamina        The distal stump, which supplies neurotrophic factors to guide elongation of axonal growth cones coming from the proximal end.        
Taking the physiology of nerve regeneration outlined above into account leads to a list of characteristics for the ideal NGC, in addition to the necessities of (i) mechanical support, (ii) linking nerve stumps, (iii) sequestering soluble factors, and (iv) preventing ingrowth of fibrotic tissue. These can include                Flexible, bio-resorbable material to prevent nerve compression as the axon re-establishes connection in the NGC lumen        Porosity to allow nutrient exchange        Pre-loading with support cells to protect against Wallerian degeneration and speed up migration time        Controlled release of chemical factors        Inclusion of a provisional matrix that is biomimetic of basal lamina and oriented to discourage nerve out-growth in undesired directions        Intralumenal channels to mimic fasicular organization of nerve bundles        Directional electrical activity to stimulate electrically active nerve cells        